Project Summary: Overall Resistance to antimicrobial therapies is a national and international crisis that threatens clinical practice from fundamental primary care to the most advanced medical interventions such as cancer chemotherapy and organ transplantation. Much of what we take for granted in clinical medicine could become too risky as microorganisms have become increasingly resistant to our newest medications and our antibiotics of last resort. Antimicrobial resistance also adds enormous costs to health care, exceeding $21 billion in the United States alone. Compounding this problem is the fact that pharmaceutical companies have largely abandoned antibiotic development programs. As an alternative to large pharmaceutical companies, academic institutions and biotech startups can step in to refill the antibiotic pipeline using novel approaches to drug discovery. The principal objective of this Phase I COBRE application is to build a unique, multi-disciplinary center of excellence to study mechanisms of antimicrobial resistance and develop therapeutic countermeasures. The long-term goal of the Center for Antimicrobial Resistance and Therapeutic Discovery (CARTD) at The Miriam Hospital of the Lifespan Hospital Group is to develop new therapies for infections caused by drug resistant pathogens. This long-term goal will be attained with shorter-term objectives of developing a new generation of junior investigators who study mechanisms of resistance, characterize new targets, and study new and existing compounds. CARTD will integrate their work with mentors and established investigators at the institution and develop core facilities to enhance research capabilities in the field of antimicrobial resistance and the discovery of new therapeutics. To achieve these objectives, the CARTD will complete the following specific aims: 1. Consolidate existing researchers into a dynamic, interactive center of excellence across The Miriam Hospital, and its academic partners in Rhode Island, including Brown University. 2. Foster the research programs and career development of junior investigators in the field of antimicrobial resistance and studies of novel therapeutic approaches. 3. Support new institutional research with pilot project funding. 4. Establish critical infrastructure with new core laboratories to facilitate cutting edge research in antimicrobial resistance and therapeutic discovery, and serve as a unique technical resources to other COBRE research programs, other institutional researchers, and investigators in the region.